NRF2 attenuation aggravates detrimental consequences of metabolic stress on cultured porcine parthenote embryos

Abstract

The nuclear factor erythroid 2–related factor 2 (NRF2) is a crucial transcription factor that plays a central role in regulating oxidative stress pathways by binding antioxidant response elements, but its involvement in early embryo development remains largely unexplored. In this study, we demonstrated that NRF2 mRNA is expressed in porcine embryos from day 2 to day 7 of development, showing a decrease in abundance from day 2 to day 3, followed by an increase on day 5 and day 7. Comparable levels of NRF2 mRNA were observed between early-cleaving and more developmental competent embryos and late-cleaving and less developmental competent embryos on day 4 and day 5 of culture. Attenuation of NRF2 mRNA significantly decreased development of parthenote embryos to the blastocyst stage. When NRF2-attenuated embryos were cultured in presence of 3.5 mM or 7 mM glucose, development to the blastocyst stage was dramatically decreased in comparison to the control group (15.9% vs. 27.8% for 3.5 mM glucose, and 5.4% vs. 25.3% for 7 mM glucose). Supplementation of melatonin moderately improved the development of NRF2-attenuated embryos cultured in presence of 0.6 mM glucose. These findings highlight the importance of NRF2 in early embryo development, particularly in embryos cultured under metabolically stressful conditions.

Bioactive Compounds Protect Mammalian Reproductive Cells from Xenobiotics and Heat Stress-Induced Oxidative Distress via Nrf2 Signaling Activation: A Narrative Review

“…Consistently, the pivotal role of Nrf2 in antioxidant defense has been well documented, highlighting its importance in combating oxidative stress and mitigating cellular damage [37,38]. In addition, the therapeutic potential of modulating Nrf2 signaling via administration of bioactive compounds to alleviate oxidative stress has garnered considerable attention in the recent literature [11,14,[39][40][41][42][43][44]. Furthermore, the Nrf2 signaling cascade, in conjunction with other protective mechanisms, is crucial in preserving the integrity of mammalian reproductive cells against oxidative stress.…”

“…This safeguarding is essential for maintaining reproductive health and function. considerable attention in the recent literature [11,14,[39][40][41][42][43][44]. Furthermore, the Nrf2 signaling cascade, in conjunction with other protective mechanisms, is crucial in preserving the integrity of mammalian reproductive cells against oxidative stress.…”